The unique combination of chemical, thermal, and mechanical stability, high fractional free volume, low refractive index, low surface energy, and wide optical transparency has led to growing interest in Teflon Amorphous Fluoropolymers (AFs) for a wide spectrum of applications ranging from chemical separations and sensors to bioassay platforms. New opportunities arise from the incorporation of nanoscale materials in Teflon AFs. In this chapter, we highlight fractional free volume - the most important property of Teflon AFs - with the aim of clarifying the unique transport behavior through Teflon AF membranes. We then review state-of-the-art developments based on Teflon AF platforms by focusing on the chemistry behind the applications.